The sex steroid hormones (estrogen and progesterone) stimulate growth, maturation and the development of new biochemical capacities in their reproductive target organs. These steroids play a major role in maternal physiology and fetal differentiation and their relationships to reproductive tissue malignancy are well established. Although steroid hormones exert major influences on the synthesis of nucleic acid and protein, the exact biochemical processes by which sex hormones regulate growth and function in target tissues are not yet clear. The general objectives of these studies are to define the mechanism of action of reproductive steroid hormones in regulating cell replication, morphologic differentiation and biochemical specialization in their target tissues. This will be accomplished by coordinating a network of separate in vivo and in vitro investigations in a single experimental animal model system in which specific biochemical events can be studied easily -- the chick oviduct. These studies will involve aspects of cell biology, nucleic acid and protein chemistry, immunology, and related intermediary metabolism; emphasis will rest heavily on regulation of nucleic acid and protein synthesis. The ultimate goal of this project is the generation of a cell-free system composed of purified reconstituted components, in which sex steroid effects on "coupled" gene transcription and translation can be completely defined. It is expected that the understanding derived from this project will be relevant to the biology of the natural reproductive hormones relative to maternal physiology, fetal development and the design of new contraceptive agents. The following proposed studies should also be pertinent to development of more precise theories for the biochemical mechanism of action of hormones in general, and more specifically steroid sex hormones. BIBLIOGRAPHIC REFERENCES: Buller, R.E., D.O. Toft, W.T. Schrader and B.W. O'Malley. Progesterone-binding components of chick oviduct: VIII. Receptor activation and hormone dependent binding to purified nuclei. J. Biol. Chem. 250: 801, 1975. Buller, R.E., W.T. Schrader and B.W. O'Malley. Progesterone-binding components of chick oviduct: IX. The kinetics of nuclear binding. J. Biol. Chem. 250:809, 1975.